1. Field of the Invention
The present invention relates generally to methods and pharmaceutical compositions for the enhanced performance of cardiopulmonary resuscitation techniques. More particularly, the present invention relates to the administration of certain pharmaceutical compositions to a patient undergoing cardiopulmonary resuscitation techniques which result in the active transport of venous blood back to the patient's thorax and heart.
Sudden cardiac arrest is a major cause of death worldwide and can arise from a variety of circumstances, including heart disease, electrical shock and other trauma, suffocation, and the like. To enhance patient survival and reduce the likelihood of damage to the brain and heart resulting from oxygen deprivation, it is essential that a patient's respiration and blood circulation be restored as soon as possible. Over the years a number of artificial resuscitation techniques have been developed with such objectives in mind.
Of particular interest to the present invention, cardiopulmonary resuscitation (CPR) techniques have been developed which rely on external chest compression. In particular, manual CPR techniques rely on the manual application of a downward force on the patient's chest in order to force blood from the heart and expel air from the lungs. Ventilation by either mouth-to-mouth or mechanical techniques is performed concurrently with the chest compression in order to force air back into the patient's lungs. Such manual CPR techniques, however, partially rely on the natural elasticity of the chest in order to actively draw venous blood back into the heart, which turns out to be highly inefficient. Long term survival in cardiac arrest patients who have undergone standard CPR is usually below 10%.
In an effort to increase the survival chances of a cardiac arrest patient, advanced cardiac life support (ACLS) techniques have been developed. Such techniques often include the intravenous or endotracheal administration of fluids and drugs, such as epinephrine, during performance of CPR. Epinephrine is an arterial constrictor, and its use is intended to enhance patient blood pressure during the resuscitation process. Even with epinephrine, however, survival after cardiac arrest is poor. Such poor survival may result from a decrease in the delivery of oxygenated blood to portions of the heart caused by epinephrine.
Venodilators, such as nitroglycerin, are drugs which dilate the coronary arteries and improve blood flow to the heart. Such venodilators are often administered to patients at risk of heart attacks in order to increase blood flow to the heart and decrease the chance of the patient suffering an attack. The use of venodilators, however, is contraindicated during the performance of most cardiopulmonary resuscitation techniques, such as CPR, since such drugs can cause a significant decrease in patient blood pressure. As such, venodilators act predominantly on the veins, it is believed that the administration of such drugs to patients undergoing CPR would result in increased pooling of blood in the veins. Thus, although venodilators are frequently administered in combination with arterial constrictors patients suffering from heart disease, the administration of such a combination to patients undergoing CPR is not practiced. Nitroglycerin is used in clinical practice when the heart is contracting but not during ventricular fibrillation, when there is a chaotic heart rhythm and no effective cardiac contractibility or blood pressure. Nitroglycerin is not currently used when the heart is not beating at all, as in asystole or electromechanical dissociation (EMD).
An improved method of CPR, referred to as active compression/decompression (ACD) CPR, results in improved blood circulation through the heart and ventilation of the patient's lungs when compared to standard CPR methods. Such ACD CPR methods utilize a vacuum cup device which is applied to the anterior chest wall and which is used for alternately compressing and "actively" expanding the patient's chest to induce both ventilation and blood circulation. By "active" expansion, it is meant that the vacuum cup adheres to the patient's chest and provides an upward force on the chest wall to expand the thorax and heart. While initial results with ACD CPR show significant improvements in patient survival rates among at least certain patient populations, it would be desirable if such survival rates could be improved even further.
It would therefore be desirable to provide improved methods and pharmaceutical compositions for performing CPR, where such methods and compositions would result in enhanced long term survival among at least certain populations of cardiac arrest patients. Such methods and compositions would preferably enhance blood circulation and delivery of oxygenated blood to patient tissue, particularly heart and/or brain tissue, without significant lessening of patient blood pressure. The compositions would preferably comprise commonly used drugs, particularly commonly used cardiovascular drugs, in novel formulations and under novel treatment regimens, preferably in combination with known CPR techniques.
2. Description of the Background Art
Conventional CPR and ACLS techniques are described in Guidelines for CPR and Emergency Cardiac Care (1992) J. Am. Med. Assoc. 268:2205-2211, where the administration of epinephrine and other arterial constrictors during cardiac arrest and the performance of CPR is described. The administration of nitroglycerin is described for the treatment of acute angina pectoris and congestive heart failure, but not during cardiac arrest concurrently with CPR and ACLS. Niemenn (1992) N. Eng. J. Med. 327:1075-1080 describes the use of arterial constrictors during CPR as part of conventional and experimental ACLS techniques. ACD CPR techniques were first described in Lurie et al. (1990) J. Am. Med. Assoc. 264:1661 and have more recently been described in Cohen et al. (1992) J. Am. Med. Assoc. 267:2916-2923. Epinephrine is commonly administered to patients undergoing ACD CPR techniques. The treatment of a patient in cardiogenic shock with the administration of nitroglycerin in combination with high-frequency positive pressure ventilation is described in Flatau et al. (1982) Isr. J. Med. Sci. 18:878-882. Kuhn (1978) Am. Heart J. 95:529-534 describe the use of nitroglycerin and other vasodilators in treatment of congestive heart failure, but warn that such vasodilators may depress already critically low arterial blood pressure. U.S.S.R. patent 1651900 describes the direct injection of nitroglycerin into the heart muscle during artificial respiration and open-heart heart massage. Other references discussing CPR and artificial respiration include Sibbald et al. (1982) Surg. Clin. N. Am. 63:455-482; and Standards and Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (1980) J. Am. Med. Assoc. 244:453-509. The full disclosures of each of these references are incorporated herein by reference.